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Influence of disodium ethane-1-hydroxy-1,1-diphosphonate on vitamin D metabolism in rats

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Summary

The metabolism and the organ distribution of double labelled vitamin D3 (1,2-3H-4-14C-cholecalciferol) has been studied in rats in which the bone mineralization and the intestinal calcium absorption have been inhibited by a large pose (10 mg P/kg s.c. for 7–14 days) of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP). The most striking difference found was a reduced accumulation of radioactive cholecalciferol and its metabolites in the kidney of EHDP-treated rats. It is unlikely that this effect was due to an unspecific alteration of the functional renal tissue since blood urea, glomerular filtration rate and renal plasm a flow remained unaltered by this dose of EHDP. The EHDP-treated rats were able to form the metabolite eluted with peak IV of the silicic acid chromatographic system, that is 25-hydroxycholecalciferol. In these vitamin D repleted rats fed a high calcium diet, the tritium deficient metabolite eluted with peak V (1,25-dihydroxycholecalciferol) was only found in the intestinal mucosa of both control and EHDP groups three days after the injection of radioactive cholecalciferol, and this in a very small amount. Therefore no definitive conclusion can be drawn as to a possible interference of EHDP treatment on the production of 1,25-dihydroxycholecalciferol. The change in the renal metabolism of vitamin D in rats treated with a rachitogenic dose of EHDP may be caused by the modifications of the calcium metabolism brought about by the diphosphonate. Its relation, if any, with the decreased calcium absorption remains to be established.

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References

  • Bligh, E. G., Dyer, W. J.: A rapid method of total lipid extraction and purification. Canad. J. Biochem. Physiol.37, 911 (1959).

    Google Scholar 

  • Blunt, J. W., Tanaka, Y., DeLuca, H. F.: The biological activity of 25-hydroxycholecalciferol, a metabolite of vitamin D. Proc. nat. Acad. Sci. (Wash.)61, 1503 (1968).

    Google Scholar 

  • Bonjour, J.-P., DeLuca, H. F., Fleisch, H., Trechsel, U., Matejowec, L. A., Omdahl, J. L.: Reversal of the EHDP inhibition of calcium absorption by 1,25-dihydroxycholecalciferol. Europ. J. clin. Invest. (in press).

  • Bonjour, J.-P., Regoli, D., Roch-Ramel, F., Peters, G.: Prerequisites for the natriuretic effect of val-5-angiotensin II amide in the rat. Amer. J. Physiol.215, 1133 (1968).

    Google Scholar 

  • Bonjour, J.-P., Russel, R. G. G., Morgan, D. B., Fleisch, H.: Intestinal calcium absorption, Ca binding protein and Ca ATPase in diphosphonate-treated rats. (Submitted).

  • Boyle, I. T., Gray, R. W., Omdahl, J. L., DeLuca, H. F.: The mechanism of adaptation of intestinal calcium absorption to low dietary calcium. J. Lab. clin. Med.78, 813 (1971).

    Google Scholar 

  • Callow, R. K., Kodicek, E., Thompson, G. A.: Metabolism of tritiated vitamin D. Proc. roy. Soc. B164, 1 (1966).

    Google Scholar 

  • Casey, P. A., Casey, G., Fleisch, H., Russel, R. G. G.: The effect of polyphloretin phosphate, polyestradiol phosphate, a diphosphonate and a polyphosphate on calcification induced by dihydrotachysterol in skin, aorta and kidney of rats. Experientia (Basel)28, 137 (1972).

    Google Scholar 

  • Fleisch, H., Russel, R. G. G., Bisaz, S., Casey, P. A., Mühlbauer, R. C.: The influence of pyrophosphate analogues (diphosphonates) on the precipitation and dissolution of calcium phosphate in vitro and in vivo. Calc. Tiss. Res2, suppl. 10 (1968).

  • Fleisch, H., Russel, R. G. G., Bisaz, S., Mühlbauer, R. C., Williams, D. A.: The inhibitory effect of phosphonates on the formation of calcium phosphate crystals in vitro and on aortic and kidney calcification in vivo. Europ. J. clin. Invest.1, 12 (1970).

    Google Scholar 

  • Francis, M. D.: The inhibition of calcium hydroxyapatite crystal growth by polyphosphonates and polyphosphates. Calc. Tiss. Res.3, 151 (1969).

    Google Scholar 

  • Francis, M. D., Russel, R. G. G., Fleisch, H.: Diphosphonates inhibit formation of calcium phosphate crystals in vitro and pathological calcification in vivo. Science165, 1264 (1969).

    Google Scholar 

  • Fraser, D. R., Kodicek, E.: Unique biosynthesis by kidney of a biologically active vitamin D metabolite. Nature (Lond.)228, 764 (1970).

    Google Scholar 

  • Gasser, A. B., Morgan, D. B., Fleisch, H. A., Richelle, L. J.: The influence of two diphosphonates on calcium metabolism in the rat. Clin. Sci.43, 31 (1972).

    Google Scholar 

  • Gray, R., Boyle, I., DeLuca, H. F.: Vitamin D metabolism: The role of kidney tissue. Science172, 1232 (1971).

    Google Scholar 

  • Hill, L. F., Mawer, E. B., Lumb, G. A., Stanbury, S. W.: The effect of diphosphonate on the metabolism and biological activity of vitamin D. Clin. Sci.42, 16 P (1972).

  • Holik, M. F., Schnoes, H. K., DeLuca, H. F.: Identification of 1,25-dihydroxycholecalciferol, a form of vitamin D3 metabolically active in the intestine. Proc. nat. Acad. Sci. (Wash.)68, 803 (1971).

    Google Scholar 

  • Holman, C. A., Mawer, E. B., Smith, D. J.: Tissue distribution of cholecalciferol (vitamin D3) in the rat. Biochem. J.170, 29 P (1970).

  • Horsting, M., DeLuca, H. F.: In vitro productions of 25-hydroxycholecalciferol. Biochem. biophys. Res. Commun.36, 251 (1969).

    Google Scholar 

  • Jowsey, J., Holley, K. E., Linman, J. W.: The effect of sodium etidronate in adult cats. J. Lab. clin. Med.76, 126 (1970).

    Google Scholar 

  • King, W. R., Francis, M. D., Michael, W. R.: Effect of disodium ethane-1-hydroxy-1,1-diphosphonate on bone formation. Clin. Orthop.78, 251 (1971).

    Google Scholar 

  • Kodicek, E., Lawson, D. E., Wilson, P. W.: Biological activity of a polar metabolite of vitamin D3. Nature (Lond.)228, 763 (1970).

    Google Scholar 

  • Lawson, D. E., Fraser, D. R., Kodicek, E., Morris, H. R., Williams, D. H.: Identification of 1,25-dihydroxycholecalciferol, a new kidney hormone controlling calcium metabolism. Nature (Lond.)230, 228 (1971).

    Google Scholar 

  • Lund, J., DeLuca, H. F.: Biologically active metabolites of vitamin D3 from bone, liver and blood serum. J. Lipid Res.7, 739 (1966).

    Google Scholar 

  • Mawer, E. B., Backhouse, J.: An improved system for the separation of metabolites of isotopically labelled vitamin D3 on silicic acid columns. Biochem. J.112, 255 (1969).

    Google Scholar 

  • Mawer, E. B., Lumb, G. A., Schaefer, K., Stanbury, S. W.: The metabolism of isotopically labelled vitamin D3 in man: the influence of the state of vitamin D nutrition. Clin. Sci.40, 39 (1971).

    Google Scholar 

  • Morgan, D. B., Bonjour, J.-P., Gasser, A. B., O'Brien, K., Fleisch, H.: The influence of a diphosphonate on the intestinal absorption of calcium. Israel J. med. Sci.7, 384 (1971).

    Google Scholar 

  • Myrtle, J. F., Norman, A. W.: Studies on calciferol metabolism. II. Tritium loss from tritiated vitamin D3 and the possible structure of the proposed nuclear regulator of intestinal calcium transport. Steroids17, 619 (1971a).

    Google Scholar 

  • Myrtle, J. F., Norman, A. W.: Vitamin D: A cholecalciferol metabolite highly active in promoting intestinal calcium transport. Science171, 79 (1971b).

    Google Scholar 

  • Neville, P. F., DeLuca, H. F.: The synthesis of [1,2-3H] vitamin D3 and the tissue localization of a 0.25 μg (10 I.U.) dose per rat. Biochemistry5, 2201 (1966).

    Google Scholar 

  • Nicolaysen, R.: The absorption of calcium as a function of the body saturation of calcium. Acta physiol. scand.5, 200 (1943).

    Google Scholar 

  • Norman, A. W., Midgett, R. J., Myrtle, J. F., Nowicki, H. G.: Studies on calciferol metabolism. I. Production of vitamin D metabolite 4 B from 25-OH-cholecalciferol by kidney homogenates. Biochem. biophys. Res. Commun.42, 1082 (1971a).

    Google Scholar 

  • Norman, A. W., Myrtle, J. F., Midgett, R. J., Nowicki, H. G., Williams, V., Popjak, G.: 1,25-dihydrocholecalciferol: Identification of the proposed form of vitamin D3 in the intestine. Science173, 51 (1971b).

    Google Scholar 

  • Olson, E. B., DeLuca, H. F.: 25-hydroxycholecalciferol: direct effect on calcium transport. Science165, 405 (1969).

    Google Scholar 

  • Ponchon, G., DeLuca, H. F.: Metabolites of vitamin D3 and their biologic activity. J. Nutr.99, 157 (1969).

    Google Scholar 

  • Ponchon, G., Kennan, A. L., DeLuca, H. F.: “Activation” of vitamin D by the liver. J. clin. Invest.48, 2032 (1969).

    Google Scholar 

  • Schnenk, R., Russel, R. G. G., Fleisch, H., Williams, D. A.: Changes in the morphology and composition of the bone in rats treated with diphosphonate. Calc. Tiss. Res. (in press).

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von Herrath, D., Schaefer, K., Bonjour, J.P. et al. Influence of disodium ethane-1-hydroxy-1,1-diphosphonate on vitamin D metabolism in rats. Pflugers Arch. 336, 249–262 (1972). https://doi.org/10.1007/BF00590049

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